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https://www.readbyqxmd.com/read/29618313/sodium-glucose-cotransporter-2-inhibitors-the-impact-on-development-and-progression-of-heart-failure
#1
Vasilios Papademetriou, Eleni Geladari
BACKGROUND: Available hypoglycemic-agents enable physicians to achieve consistent glycemic-control, but effects on cardiovascular-outcomes have been marginal or questionable. SGLT-2 inhibitors emerged as a novel antidiabetic-drug class with remarkable cardiovascular benefits, and significant improvement in the prevention and progression of HF. OBJECTIVE: The purpose of this article is to critically review the effect of SGLT-2 inhibitors on HF-outcomes and the potential underlying mechanisms...
April 4, 2018: Cardiovascular & Hematological Disorders Drug Targets
https://www.readbyqxmd.com/read/29602453/sglt2-inhibitor-induced-euglycaemic-diabetic-ketoacidosis-may-be-due-to-abrupt-severe-and-transient-impaired-glucose-sensing-in-susceptible-individuals-with-a-hitherto-unrecognised-beta-cell-sglt-variant
#2
F M Finucane
Euglycaemic diabetic ketoacidosis (EDKA) is a rare complication of treatment with SGLT2 inhibitors in patients with type 2 diabetes. Uncertainty remains about its precise mechanistic basis, but the physiological derangement is acute and profound, yet reversible with cessation of the drug. It is reminiscent of other "non type 1" presentations with DKA such as ketosis prone diabetes, except that glucose levels are usually normal. Impaired beta cell glucose sensing that mimicked a state of hypoglycaemia could theoretically lead to abrupt and transient cessation of insulin secretion...
May 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29589183/new-diabetes-therapies-and-diabetic-kidney-disease-progression-the-role-of-sglt-2-inhibitors
#3
REVIEW
Claire C J Dekkers, Ron T Gansevoort, Hiddo J L Heerspink
PURPOSE OF REVIEW: Sodium-glucose co-transporter 2 (SGLT-2) inhibitors have emerged as a promising drug class for the treatment of diabetic kidney disease. Developed originally as glucose-lowering drugs by enhancing urinary glucose excretion, these drugs also lower many other renal and cardiovascular risk factors such as body weight, blood pressure, albuminuria, and uric acid. Results from the EMPA-REG OUTCOME and CANVAS trials show that these salutary effects translate into a reduction in cardiovascular outcomes and have the potential to delay the progression of kidney function decline...
March 27, 2018: Current Diabetes Reports
https://www.readbyqxmd.com/read/29589153/an-exploratory-study-of-dapagliflozin-for-the-attenuation-of-albuminuria-in-patients-with-heart-failure-and-type-2-diabetes-mellitus-dapper
#4
Fumiki Yoshihara, Miki Imazu, Toshimitsu Hamasaki, Toshihisa Anzai, Satoshi Yasuda, Shin Ito, Haruko Yamamoto, Kazuhiko Hashimura, Yoshio Yasumura, Kiyoshi Mori, Masataka Watanabe, Masanori Asakura, Masafumi Kitakaze
BACKGROUND AND AIMS: Sodium-dependent glucose transporter-2 (SGLT-2) inhibitors, which are anti-diabetic drugs, reportedly decrease the incidence of cardiovascular events in high-risk patients with cardiovascular diseases, and thus chronic heart failure (CHF). SGLT-2 inhibitors also decrease albuminuria in patients with type 2 diabetes mellitus (T2D). Since albuminuria is a biomarker of not only chronic kidney disease but also cardiovascular events, we hypothesized that, among T2D patients with CHF, SGLT-2 inhibitors will decrease the extent of albuminuria and also improve CHF concomitantly...
March 28, 2018: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/29573529/effects-of-the-sglt-2-inhibitor-dapagliflozin-on-glomerular-and-tubular-injury-markers
#5
Claire C J Dekkers, Sergei Petrykiv, Gozewijn Laverman, David Z Cherney, Ron T Gansevoort, Hiddo J L Heerspink
The mechanisms by which SGLT-2 inhibitors lower albuminuria are incompletely understood. We assessed in a post-hoc analysis of a cross-over trial effects of the SGLT2 inhibitor dapagliflozin on glomerular markers (IgG to IgG4 and IgG to albumin), tubular markers (urinary KIM-1, NGAL, and LFABP) and inflammatory markers (urinary MCP-1 and IL-6) to provide more insight into kidney protective effects. Dapagliflozin decreased albuminuria by 43.9% (95% CI: 30.3 to 54.8%) and eGFR by 5.1 (2.0 to 8.1) ml/min/1.73m2 compared to placebo...
March 24, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29569427/sodium-glucose-co-transporter-2-inhibitors-and-the-risk-for-diabetic-ketoacidosis-in-patients-with-type-2-diabetes-mellitus-a-nationwide-population-based-cohort-study
#6
Young-Gun Kim, Ja Young Jeon, Seung Jin Han, Dae Jung Kim, Kwan-Woo Lee, Hae Jin Kim
AIMS: The risk for diabetic ketoacidosis (DKA) associated with sodium-glucose co-transporter-2 inhibitor (SGLT-2i) treatment has not been established. Thus, we aimed to estimate the risk for DKA associated with SGLT-2i treatment compared to that with dipeptidyl-peptidase IV inhibitor (DPP-4i) treatment. METHODS: A nationwide population-based cohort study using claims data of the Korean Health Insurance Review and Assessment Service from January 1, 2013 to June 30, 2017 was performed...
March 22, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29569378/rates-of-myocardial-infarction-and-stroke-in-patients-initiated-on-sglt2-inhibitors-versus-other-glucose-lowering-agents-in-real-world-clinical-practice-results-from-the-cvd-real-study
#7
Mikhail Kosiborod, Kåre I Birkeland, Matthew A Cavender, Alex Z Fu, John P Wilding, Kamlesh Khunti, Reinhard W Holl, Anna Norhammar, Marit Eika Jørgensen, Eric T Wittbrodt, Marcus Thuresson, Johan Bodegård, Niklas Hammar, Peter Fenici
The multinational, observational CVD-REAL study recently showed that initiation of sodium-glucose co-transporter-2 inhibitors (SGLT-2i) was associated with significantly lower rates of death and heart failure vs. other glucose-lowering drugs (oGLDs). This sub-analysis of CVD-REAL sought to determine the association between initiation of SGLT-2i vs. oGLDs and rates of myocardial infarction (MI) and stroke. Medical records, claims and national registers from the US, Sweden, Norway and Denmark were used to identify patients with T2D newly initiated on SGLT-2i (canagliflozin, dapagliflozin or empagliflozin) or oGLDs...
March 22, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29554671/review-adding-a-dpp-4-inhibitor-to-an-sglt-2-inhibitor-reduces-genital-but-not-genitourinary-tract-infections
#8
René Rodriguez-Gutierrez, Victor M Montori
No abstract text is available yet for this article.
March 20, 2018: Annals of Internal Medicine
https://www.readbyqxmd.com/read/29542418/diabetic-ketoacidosis-in-patients-with-type-2-diabetes-on-sodium-glucose-cotransporter-2-inhibitors-a-case-series
#9
Purva Sharma, Yash Jobanputra, Karen Lewin, Stuart Bagatell, Daniel Lichtstein
BACKGROUND: Diabetic ketoacidosis (DKA) is a serious complication of diabetes seen commonly in autoimmune Type 1 diabetes mellitus (DM), however patients with Type 2 diabetes are also at risk. Diabetic ketoacidosis may be precipitated by the catabolic stress of acute illness such as trauma, surgery, or infections. Recent studies have suggested that sodium glucose cotransporter-2 (SGLT-2) inhibitors precipitate DKA in Type 2 diabetes. We present a case series of four patients on SGLT-2 inhibitors who presented with DKA...
March 13, 2018: Reviews on Recent Clinical Trials
https://www.readbyqxmd.com/read/29540325/lower-cardiovascular-risk-associated-with-sglt-2i-in-400-000-patients-the-cvd-real-2-study
#10
Mikhail Kosiborod, Carolyn S P Lam, Shun Kohsaka, Dae Jung Kim, Avraham Karasik, Jonathan Shaw, Navdeep Tangri, Su-Yen Goh, Marcus Thuresson, Hungta Chen, Filip Surmont, Niklas Hammar, Peter Fenici
BACKGROUND: Randomized trials demonstrated lower risk of cardiovascular (CV) events with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) in patients with type 2 diabetes (T2D) at high CV risk. Prior real-world data suggested similar SGLT-2i effects in T2D patients with broader risk profile, but focused on heart failure and death, and were limited to US and Europe. OBJECTIVES: To examine a broad range of CV outcomes in patients initiated on SGLT-2i vs. other glucose lowering drugs (oGLD) across six countries in Asia Pacific, Middle East and North America (NCT02993614)...
March 7, 2018: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29525972/positron-emission-tomography-of-sodium-glucose-cotransport-activity-in-high-grade-astrocytomas
#11
Vladimir Kepe, Claudio Scafoglio, Jie Liu, William H Yong, Marvin Bergsneider, Sung-Cheng Huang, Jorge R Barrio, Ernest M Wright
A novel glucose transporter, the sodium glucose cotransporter 2 (SGLT2), has been demonstrated to contribute to the demand for glucose by pancreatic and prostate tumors, and its functional activity has been imaged using a SGLT specific PET imaging probe, α-methyl-4-[F-18]fluoro-4-deoxy-D-glucopyaranoside (Me-4FDG). In this study, Me-4FDG PET was extended to evaluate patients with high-grade astrocytic tumors. Me-4FDG PET scans were performed in four patients diagnosed with WHO Grade III or IV astrocytomas and control subjects, and compared with 2-deoxy-2-[F-18]fluoro-D-glucose (2-FDG) PET and magnetic resonance imaging (MRI) of the same subjects...
March 10, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29516618/sodium-glucose-co-transporter-2-inhibitors-sglt2is-the-latest-residents-on-the-block-impact-on-glycaemic-control-at-a-general-practice-level-in-england
#12
A H Heald, A A Fryer, S G Anderson, M Livingston, M Lunt, M Davies, Gyc Moreno, R Gadsby, R J Young, M Stedman
AIMS: Despite increasing spend on new Type 2 diabetes mellitus (T2DM) therapies, the proportion of people with T2DM achieving target glycaemia outcomes is declining. Our aim was to determine, using published General Practice level data, how differences in T2DM prescribing patterns relate to glycaemic target achievement levels. METHODS: Multiple linear regression modelling was used to link practice characteristics and defined daily dose (DDD) of class of medication in 2015/16 and changes to 2014/15 in medication to proportions achieving target glycaemic control (TGC; glycated haemoglobin A1c (HbA1c) ≤7...
March 8, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29516612/use-and-effectiveness-of-dapagliflozin-in-routine-clinical-practice-an-italian-multicenter-retrospective-study
#13
Gian Paolo Fadini, Giancarlo Zatti, Ileana Baldi, Daniele Bottigliengo, Agostino Consoli, Andrea Giaccari, Giorgio Sesti, Angelo Avogaro
In randomized controlled trials (RCTs), SGLT-2 inhibitors (SGLT2i) showed glycaemic and extra-glycaemic benefits. The DARWIN-T2D (DApagliflozin Real World evIdeNce in Type 2 Diabetes) was a multicenter retrospective study designed to evaluate baseline characteristics of patients receiving dapagliflozin versus selected comparators (DPP-4 inhibitors, gliclazide, or GLP-1 receptor agonists), and drug effectiveness in routine clinical practice. From a population of 281,217 patients, the analysis included 17,285 initiating dapagliflozin or comparator glucose lowering medications (GLM), 6751 of whom had a follow-up examination...
March 8, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29512713/role-of-sglt1-in-high-glucose-level-induced-mmp-2-expression-in-human-cardiac-fibroblasts
#14
Liping Meng, Hiroyasu Uzui, Hangyuan Guo, Hiroshi Tada
Cardiac fibrosis is a major pathological manifestation of diabetic cardiomyopathy (DCM), which leads to cardiac remodeling, dilated cardiomyopathy and congestive heart failure. Human cardiac fibroblasts (HCF) constitute the predominant cell type in the heart and matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are also involved in cardiac fibrosis. However, it is unclear whether high glucose levels affect the expression of MMPs and TIMPs in HCF. Sodium‑glucose cotransporter (SGLT) inhibitors have been developed as therapeutic agents and the anti‑DCM effect of SGLT inhibitors has been demonstrated by previous studies...
March 6, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29485012/sodium-glucose-cotransporter-2-inhibitors-potential-cardiovascular-and-mortality-benefits
#15
Lovic Dragan, Manolis Kallistratos, Constantinos Tsioufis, Charalampos Grassos, Dragan Djordjevic, Ivan Tasic, Athanasios Manolis, Andreas Pittaras
BACKGROUND: The impact of overt diabetes and poor glycemic control on the risk of cardiovascular disease is well established. Among patients with type 2 diabetes, several studies demonstrated a significant increase in coronary artery disease related death and cardiovacular events associated with HbA1c levels of greater than 7 % compared with lower levels. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are a novel class of anti-diabetic drugs that lower blood glucose levels through the suppression of renal glucose reabsorption thereby promoting renal glucose excretion...
February 26, 2018: Cardiovascular & Hematological Disorders Drug Targets
https://www.readbyqxmd.com/read/29484489/sglt-2-inhibitors-and-the-risk-of-infections-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#16
Robert Puckrin, Marie-Philippe Saltiel, Pauline Reynier, Laurent Azoulay, Oriana H Y Yu, Kristian B Filion
AIMS: There is concern about the infection-related safety profile of sodium-glucose co-transporter 2 (SGLT-2) inhibitors. We aimed to determine the effect of SGLT-2 inhibitors on genitourinary and other infections via systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: We conducted a systematic search of Medline, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov to identify double-blinded RCTs enrolling ≥ 50 patients with type 2 diabetes which compared an SGLT-2 inhibitor to placebo or active comparator...
February 27, 2018: Acta Diabetologica
https://www.readbyqxmd.com/read/29477576/sodium-glucose-cotransporter-2-inhibitors-induced-eu-glycemic-diabetic-ketoacidosis-the-first-report-in-a-type-2-diabetic-t2d-taiwanese-and-literature-review-of-possible-pathophysiology-and-contributing-factors
#17
Yi-Hsin Lin
Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are the newest class of oral antidiabetic drugs (OADs), approved to be a second-line OAD for type 2 diabetes in Taiwan since 2016. The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) had both released statements associating the use of SGLT-2 inhibitors may increase the risk of eu-glycemic diabetic ketoacidosis (euDKA). This review reveals the possible pathophysiology with a chain of metabolic adaptions to decrease plasma glucose and increase plasma ketone bodies through pancreas, kidney, liver and adipose tissue...
February 21, 2018: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/29477373/comparing-sglt-2-inhibitors-to-dpp-4-inhibitors-as-an-add-on-therapy-to-metformin-in-patients-with-type-2-diabetes-a-systematic-review-and-meta-analysis
#18
REVIEW
B M Mishriky, R J Tanenberg, K A Sewell, D M Cummings
AIMS: Our aim was to compare Sodium-glucose co-transporter 2 inhibitors (SGLT-2i) to Dipeptidyl peptidase-4 inhibitors (DPP-4i) as add-on therapy to metformin. METHODS: We searched for randomized trials comparing SGLT-2i to DPP-4i as add-on therapy to metformin in Type 2 diabetes.We pooled trials reporting outcomes between 12 and 26 weeks together while trials reporting results ≥52 weeks were pooled together. The primary outcomes were the change in haemoglobin A1c (A1c) at ≤26 and ≥52 weeks...
February 7, 2018: Diabetes & Metabolism
https://www.readbyqxmd.com/read/29476696/treatment-of-a-case-of-severe-insulin-resistance-due-to-a-pik3r1-mutation-with-a-sodium-glucose-cotransporter-2-inhibitor
#19
Tetsushi Hamaguchi, Yushi Hirota, Takehito Takeuchi, Yasushi Nakagawa, Atsuko Matsuoka, Masaaki Matsumoto, Hiroyuki Awano, Kazumoto Iijima, Pei Chieng Cha, Wataru Satake, Tatsushi Toda, Wataru Ogawa
A Japanese woman in her late 30s with severe insulin resistance and bodily features including a triangular face, prominent forehead, small chin, large and low-set ears, and ocular depression was investigated. A similar phenotype was not observed in other family members with the exception of her son, suggesting that the condition was caused by a de novo mutation that was transmitted from mother to son. Exome analysis revealed the presence in the proband and her son of a c.1945C>T mutation in PIK3R1, a common mutation associated with SHORT syndrome...
February 24, 2018: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29451721/sodium-glucose-co-transporter-2-sglt2-inhibitors-as-add-on-therapy-to-insulin-for-type-1-diabetes-mellitus-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#20
Tomohide Yamada, Nobuhiro Shojima, Hisashi Noma, Toshimasa Yamauchi, Takashi Kadowaki
New treatments for type 1 diabetes are an unmet need. We investigated the efficacy and safety of adding SGLT-2is to insulin for type 1 diabetes by meta-analysis of prospective randomized, placebo-controlled trials. Searching electronic databases up to October 2017 identified 1361 studies, among which 14 were investigated (N=4,591). Meta-analysis revealed that SGLT-2i therapy significantly reduced HbA1c by 0.4% (95% confidence interval [CI]: 0.35, 0.46; P<0.001; I2=0%), fasting plasma glucose by 1.14 mmol/l (0...
February 16, 2018: Diabetes, Obesity & Metabolism
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